In this application, we propose a Clinical Proteomic Technology Assessment for Cancer (CPTAC) program at Vanderbilt University, which will work as part of the NCI CPTAC consortium to compare, improve, and standardize proteomic technologies for clinical cancer research. The rapid advance of mass spectrometry (MS) and related technologies offers powerful new tools to analyze proteomes. Recent work indicates that distinct patterns of proteome expression characterize not only different cancers but also distinguish phenotypes that reflect the course of disease and response to therapy. The Vanderbilt CPTAC will address three broad goals. First, shotgun proteome methods will be improved in both throughput and reproducibility and standardized both in analytical methods and data analysis. Second, targeted quantitative analyses by stable isotope dilution LC-MS-MS and reverse phase antibody array technology will be used to quantify candidate markers. Third, these platforms and accompanying data analysis tools will be standardized to enable interlaboratory collaborations in biomarker discovery and analysis. Initial work will employ mouse models of human cancer for technology development and validation. The Vanderbilt CPTAC program will also collect clinical specimens from patients with breast, lung, and colorectal cancers, and these specimens will be used to define the application of shotgun proteome analysis platforms to discovery and quantitation of cancer biomarkers. We will work with the NCI and members of the CPTAC to develop well defined and comprehensively characterized sets of standard/reference materials, reagents, and bioinformatics tools to serve as resources for the research community.